Herpesvirus saimiri is an oncogenic herpesvirus of New World primates. We will use h. saimiri as a representative of the gamma herpesviruses to express SIV antigens for vaccine purposes. We have chosen h. saimiri because it is distinct from herpes simplex virus, an alpha herpesvirus, because of its ability to infect rhesus monkeys and for the relative ease with which its genome can be manipulated. We will first identify an appropriate h. saimiri gene that, when deleted, yields replication- competent, nonpathogenic virus that is able to persist in rhesus monkeys. Candidate genes based on previous studies include STP (saimiri transformation-associated protein), ORF-1, v-cyclin and superantigen homolog. We will then construct recombinant h. saimiri strains expressing SIV antigens by replacing the selected target gene with an SIV gene or genes. Recombinant strains expressing SIV env, gag-pol, and env+gag-pol will be separately constructed and analyzed. H. saimiri and SV40 promoters will be compared for their ability to direct SIV antigen expression from within the h. saimiri genome. Well-characterized, recombinant h. saimiri strains expressing SIV antigens derived from these studies will be used for vaccine testing in the project by Ronald C. Desrosiers.